当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi.

Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi.

Abstract：

:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds that were effective against the enzymes and the parasites but also some compounds that were parasiticidal despite a lack of activity against the proteases. Several compounds were effective in killing all tested parasites. These promising lead compounds were tested for general toxicity in mice, and only one produced observable toxicity after 62 h. Our results suggest that thiosemicarbazones represent validated drug leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as other novel targets.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Greenbaum DC,Mackey Z,Hansell E,Doyle P,Gut J,Caffrey CR,Lehrman J,Rosenthal PJ,McKerrow JH,Chibale K

doi

10.1021/jm030549j

keywords:

subject

Has Abstract

pub_date

2004-06-03 00:00:00

pages

3212-9

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

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